Changes in the bacterial flora of the neoterminal ileum after ileocolonic resection for Crohn's disease

Neut, Christel; Bulois, P.; Desreumaux, Pierre; Membré, Jeanne‐Marie; Lederman, Emmanuel; Gambiez, L; Cortot, Antoine; Quandallé, P; Kruiningen, Herbert Van; Colombel, Jean–Frédéric

doi:10.1111/j.1572-0241.2002.05613.x

Cited by 240 publications

(126 citation statements)

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“…Most E. coli strains isolated from the ileal mucosa of CD patients are able to adhere to and invade intestinal epithelial cells (14)(15)(16) and belong to the pathogenic group of adherent invasive E. coli (AIEC) (17). AIEC is highly associated with the ileal mucosa in CD patients (14)(15)(16)(18)(19)(20)(21)(22)(23). CD-associated AIEC cells adhere to the brush border of primary ileal enterocytes isolated from CD patients but not to enterocytes isolated from controls without inflammatory bowel disease.…”

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confidence: 99%

Ribonucleotide Reductase NrdR as a Novel Regulator for Motility and Chemotaxis during Adherent-Invasive Escherichia coli Infection

et al. 2015

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A critical step in the life cycle of all organisms is the duplication of the genetic material during cell division. Ribonucleotide reductases (RNRs) are essential enzymes for this step because they control the de novo production of the deoxyribonucleotides required for DNA synthesis and repair. Enterobacteriaceae have three functional classes of RNRs (Ia, Ib, and III), which are transcribed from separate operons and encoded by the genes nrdAB, nrdHIEF, and nrdDG, respectively. Here, we investigated the role of RNRs in the virulence of adherent-invasive Escherichia coli (AIEC) isolated from Crohn's disease (CD) patients. Interestingly, the LF82 strain of AIEC harbors four different RNRs (two class Ia, one class Ib, and one class III). Although the E. coli RNR enzymes have been extensively characterized both biochemically and enzymatically, little is known about their roles during bacterial infection. We found that RNR expression was modified in AIEC LF82 bacteria during cell infection, suggesting that RNRs play an important role in AIEC virulence. Knockout of the nrdR and nrdD genes, which encode a transcriptional regulator of RNRs and class III anaerobic RNR, respectively, decreased AIEC LF82's ability to colonize the gut mucosa of transgenic mice that express human CEACAM6 (carcinoembryonic antigen-related cell adhesion molecule 6). Microarray experiments demonstrated that NrdR plays an indirect role in AIEC virulence by interfering with bacterial motility and chemotaxis. Thus, the development of drugs targeting RNR classes, in particular NrdR and NrdD, could be a promising new strategy to control gut colonization by AIEC bacteria in CD patients.R ibonucleotide reductase (RNR) is an essential enzyme in all living organisms. It catalyzes the reduction of ribonucleotides (nucleoside triphosphates [NTPs]) to their corresponding 2=-deoxyribonucleotides (deoxynucleoside triphosphates [dNTPs]) and therefore plays an essential role in DNA synthesis and repair. Three RNR classes (classes I, II, and III) exist; these classes exhibit different primary structures, subunit cofactor requirements, and quaternary three-dimensional (3D) structures, but they all are allosterically regulated and share similar catalytic mechanisms (1, 2). Class I RNRs are oxygendependent enzymes that occur in eubacteria, eukaryotes, and some viruses. This class comprises two main subgroups (Ia and Ib). Class Ia RNRs are encoded by an operon containing nrdA and nrdB genes. These genes encode the NrdA subunit, which is catalytically and allosterically regulated, and the NrdB subunit, which possesses radical-generating activity. Class Ib RNRs are encoded by an operon containing the nrdH, nrdI, nrdE, and nrdF genes, which encode the corresponding specific redoxin NrdH, the activating subunit NrdI, the catalytic subunit NrdE, and the radical-generating subunit NrdF. Class III RNRs are present in facultative anaerobic and strict anaerobic microorganisms and use S-adenosylmethionine and iron-sulfur clusters in the NrdG accessory protein to create a stab...

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Ribonucleotide Reductase NrdR as a Novel Regulator for Motility and Chemotaxis during Adherent-Invasive Escherichia coli Infection

et al. 2015

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“…As bacteria are one of the most abundant components of the intestinal lumen, numerous studies have investigated the composition of the luminal and mucosal enteric microbiota of IBD patients [18,19,20,21,22,23]. Increased concentrations of mucosal bacteria have been found as well as an altered composition of the microbiota, called dysbiosis [22,23].…”

Section: Why Antibacterial Treatment Makes Sensementioning

confidence: 99%

The Role of Anti(myco)bacterial Interventions in the Management of IBD: Is There Evidence at All?

Chambrun¹,

Torres

Darfeuille‐Michaud

et al. 2012

Dig Dis

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Background/Aims: The etiology of IBD is unknown but may relate to an unidentified bacterial pathogen or an immunological reaction to gut microbiota. Antibiotics have therefore been proposed as a therapy for Crohn’s disease (CD) and ulcerative colitis (UC). The aim of this review was to compel the evidence for the use of antibiotics in the treatment of IBD. Methods: We performed a systematic review of the literature regarding the use of antibiotics for inducing or maintaining remission in IBD. Results: Current data are conflicting, but a recent systematic review of randomized controlled trials has shown a statistically significant effect of antibiotics being superior to placebo for active, perianal and quiescent CD and for active UC. These data have been poorly translated in clinical practice and the place of antibiotics is restricted to certain specific situations in the international guidelines. This is first linked to the difficulties in interpreting clinical trials because of their heterogeneity in study design, endpoints, type of antibiotic and concomitant therapies. The exception to this is the use of either ciprofloxacin or metronidazole for treating CD perianal fistulas. Conclusion: The pathology of CD, the likely primary and known secondary pathogens in this disease and the successful responses in animal models all plead for new trials of antibiotics in IBD. This is a call to select patients more carefully, and to continue antibiotics for longer than is customary. Beside antibiotics, new therapeutic approaches that can balance gut dysbiosis should be tested.

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“…4-7 While there is supportive evidence that species from the Bacteroidales order are associated with decreased incidence of colitis in patients administered anti-CTLA-4 Ab, 8 there is also data correlating the colonization of certain Bacteroidales species in the gut with colitis 9 , 10 and Crohn's disease. 11 , 12 Inconsistencies and multiple variables in comparative research force the analysis of factors which might confound the results in this publication, including the possibility of antibiotic resistance and inexplicit microbial baseline values in antibiotic-treated mice models. 13 Additionally, while mice models are crucial, as they enable experimental procedures that cannot be replicated easily in humans, data extrapolation from mice studies into humans is difficult and fraught to repeat and transfer without accumulating additional variables.…”

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confidence: 99%

The gut microbiota and immune checkpoint inhibitors

Humphries

Daud

2018

Human Vaccines & Immunotherapeutics

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Although immunotherapy has been remarkably effective across multiple cancer types, there continues to be a significant number of non-responding patients. A possible factor proposed to influence the efficacy of immunotherapies is the gut microbiome. We discuss the results and implications of recent research on the relationship between the gut microbiome, our immune systems, and immune checkpoint inhibitor therapies including anti-CTLA-4 Ab and anti-PD-1 Ab. While the investigations all exhibit interesting results and conclusions, we find little congruence in the specific bacteria that were found favorable for antitumor responses. It is unclear whether the inconsistencies are due to differential approaches in study design (pre-clinical or clinical subjects, anti-CTLA-4 Ab or anti-PD-1 Ab), experimental methods and measurements (metagenomics sequencing and clustering variations) or subject population dynamics (differential cancer types and baseline characteristics). Moreover, we note studies regarding particular bacterial commensals and autoimmune diseases, which challenge findings from these investigations. We conclude that with the current research, clinical investigators can appreciate the critical role of gut microbiota in mediating immunostimulant response. However, prospective research exploring the biochemical mechanisms which commensal bacteria communicate with each other and the immune system is imperative to understand how they can be adjusted properly for higher immunotherapy response.

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Changes in the bacterial flora of the neoterminal ileum after ileocolonic resection for Crohn's disease

Abstract: After ileocolectomy, colonization of the neoterminal ileum is increased. Our data suggest that increases in the populations of specific bacteria such as E. coli, enterococci, bacteroides, and fusobacteria may be important in postoperative recurrence of Crohn's disease.

Cited by 240 publications

References 42 publications

Ribonucleotide Reductase NrdR as a Novel Regulator for Motility and Chemotaxis during Adherent-Invasive Escherichia coli Infection

Ribonucleotide Reductase NrdR as a Novel Regulator for Motility and Chemotaxis during Adherent-Invasive Escherichia coli Infection

The Role of Anti(myco)bacterial Interventions in the Management of IBD: Is There Evidence at All?

The gut microbiota and immune checkpoint inhibitors

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